Skip to main content
Erschienen in: Pediatric Nephrology 3/2018

23.10.2017 | Original Article

Preoperative levels of urinary uromodulin predict acute kidney injury after pediatric cardiopulmonary bypass surgery

verfasst von: Michael R. Bennett, Olivia Pyles, Qing Ma, Prasad Devarajan

Erschienen in: Pediatric Nephrology | Ausgabe 3/2018

Einloggen, um Zugang zu erhalten

Abstract

Background

Acute kidney injury (AKI) is a common complication of cardiopulmonary bypass surgery (CPB) in children. Several promising postoperative AKI biomarkers have been identified, but no preoperative biomarkers are available. We evaluated the association of urinary uromodulin (uUMOD) with postoperative AKI.

Methods

One hundred and one children undergoing CPB were enrolled. Urine was collected prior to CPB, and AKI was defined as ≧50% increase in serum creatinine from preoperative baseline within 48 h of surgery.

Results

Forty-seven patients (47%) developed AKI, and 92% of participants in the lowest quartile of preoperative uUMOD concentrations developed AKI compared with 8% in the highest quartile. Patients with preoperative uUMOD levels in the lowest quartile had 132.3× increased risk of postoperative AKI versus the highest quartile. Raw uUMOD levels were significantly lower in patients with AKI vs. no AKI. Significance was unchanged after correcting uUMOD levels for urinary creatinine. Receiver operating characteristic analysis showed preoperative uUMOD strongly predicted postoperative AKI, with area under the curve (AUC) 0.90. Stepwise logistic regression analysis revealed a model combining uUMOD, and bypass time predicted AKI at p<0.001. Neither Risk Adjustment for Congenital Heart Surgery 1 (RACHS) score nor age improved the model’s ability to predict AKI. Independent analysis demonstrated that while bypass time was associated with AKI, the predictive ability of bypass time (AUC 0.77) was less than that of preoperative uUMOD levels (AUC 0.9).

Conclusions

Children with lowest preoperative levels of uUMOD have greatly increased risk of AKI post-CPB. If uUMOD were used to risk-stratify patients undergoing CPB, clinical measures could be taken to minimize AKI development.
Literatur
1.
Zurück zum Zitat Li S, Krawczeski CD, Zappitelli M, Devarajan P, Thiessen-Philbrook H, Coca SG, Kim RW, Parikh CR, TRIBE-AKI Consortium (2011) Incidence, risk factors, and outcomes of acute kidney injury after pediatric cardiac surgery: a prospective multicenter study. Crit Care Med 39:1493–1499CrossRefPubMedPubMedCentral Li S, Krawczeski CD, Zappitelli M, Devarajan P, Thiessen-Philbrook H, Coca SG, Kim RW, Parikh CR, TRIBE-AKI Consortium (2011) Incidence, risk factors, and outcomes of acute kidney injury after pediatric cardiac surgery: a prospective multicenter study. Crit Care Med 39:1493–1499CrossRefPubMedPubMedCentral
3.
Zurück zum Zitat Pedersen KR, Povlsen JV, Christensen S, Pedersen J, Hjortholm K, Larsen SH, Hjortdal VE (2007) Risk factors for acute renal failure requiring dialysis after surgery for congenital heart disease in children. Acta Anaesthesiol Scand 51:1344–1349CrossRefPubMed Pedersen KR, Povlsen JV, Christensen S, Pedersen J, Hjortholm K, Larsen SH, Hjortdal VE (2007) Risk factors for acute renal failure requiring dialysis after surgery for congenital heart disease in children. Acta Anaesthesiol Scand 51:1344–1349CrossRefPubMed
4.
Zurück zum Zitat Picca S, Principato F, Mazzera E, Corona R, Ferrigno L, Marcelletti C, Rizzoni G (1995) Risks of acute renal failure after cardiopulmonary bypass surgery in children: a retrospective 10-year case-control study. Nephrol Dial Transplant 10:630–636PubMed Picca S, Principato F, Mazzera E, Corona R, Ferrigno L, Marcelletti C, Rizzoni G (1995) Risks of acute renal failure after cardiopulmonary bypass surgery in children: a retrospective 10-year case-control study. Nephrol Dial Transplant 10:630–636PubMed
5.
Zurück zum Zitat Dittrich S, Dahnert I, Vogel M, Stiller B, Haas NA, Alexi-Meskishvili V, Lange PE (1999) Peritoneal dialysis after infant open heart surgery: observations in 27 patients. Ann Thorac Surg 68:160–163CrossRefPubMed Dittrich S, Dahnert I, Vogel M, Stiller B, Haas NA, Alexi-Meskishvili V, Lange PE (1999) Peritoneal dialysis after infant open heart surgery: observations in 27 patients. Ann Thorac Surg 68:160–163CrossRefPubMed
6.
Zurück zum Zitat Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, Ruff SM, Zahedi K, Shao M, Bean J, Mori K, Barasch J, Devarajan P (2005) Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 365:1231–1238CrossRefPubMed Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, Ruff SM, Zahedi K, Shao M, Bean J, Mori K, Barasch J, Devarajan P (2005) Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 365:1231–1238CrossRefPubMed
7.
Zurück zum Zitat Mishra J, Ma Q, Prada A, Mitsnefes M, Zahedi K, Yang J, Barasch J, Devarajan P (2003) Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. J Am Soc Nephrol 14:2534–2543CrossRefPubMed Mishra J, Ma Q, Prada A, Mitsnefes M, Zahedi K, Yang J, Barasch J, Devarajan P (2003) Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. J Am Soc Nephrol 14:2534–2543CrossRefPubMed
8.
Zurück zum Zitat Parikh CR, Mishra J, Thiessen-Philbrook H, Dursun B, Ma Q, Kelly C, Dent C, Devarajan P, Edelstein CL (2006) Urinary IL-18 is an early predictive biomarker of acute kidney injury after cardiac surgery. Kidney Int 70:199–203CrossRefPubMed Parikh CR, Mishra J, Thiessen-Philbrook H, Dursun B, Ma Q, Kelly C, Dent C, Devarajan P, Edelstein CL (2006) Urinary IL-18 is an early predictive biomarker of acute kidney injury after cardiac surgery. Kidney Int 70:199–203CrossRefPubMed
9.
Zurück zum Zitat Krawczeski CD, Goldstein SL, Woo JG, Wang Y, Piyaphanee N, Ma Q, Bennett M, Devarajan P (2011) Temporal relationship and predictive value of urinary acute kidney injury biomarkers after pediatric cardiopulmonary bypass. J Am Coll Cardiol 58:2301–2309CrossRefPubMedPubMedCentral Krawczeski CD, Goldstein SL, Woo JG, Wang Y, Piyaphanee N, Ma Q, Bennett M, Devarajan P (2011) Temporal relationship and predictive value of urinary acute kidney injury biomarkers after pediatric cardiopulmonary bypass. J Am Coll Cardiol 58:2301–2309CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Endre ZH, Pickering JW, Walker RJ, Devarajan P, Edelstein CL, Bonventre JV, Frampton CM, Bennett MR, Ma Q, Sabbisetti VS, Vaidya VS, Walcher AM, Shaw GM, Henderson SJ, Nejat M, Schollum JB, George PM (2011) Improved performance of urinary biomarkers of acute kidney injury in the critically ill by stratification for injury duration and baseline renal function. Kidney Int 79:1119–1130CrossRefPubMed Endre ZH, Pickering JW, Walker RJ, Devarajan P, Edelstein CL, Bonventre JV, Frampton CM, Bennett MR, Ma Q, Sabbisetti VS, Vaidya VS, Walcher AM, Shaw GM, Henderson SJ, Nejat M, Schollum JB, George PM (2011) Improved performance of urinary biomarkers of acute kidney injury in the critically ill by stratification for injury duration and baseline renal function. Kidney Int 79:1119–1130CrossRefPubMed
11.
Zurück zum Zitat Parikh CR, Devarajan P, Zappitelli M, Sint K, Thiessen-Philbrook H, Li S, Kim RW, Koyner JL, Coca SG, Edelstein CL, Shlipak MG, Garg AX, Krawczeski CD (2011) Postoperative biomarkers predict acute kidney injury and poor outcomes after pediatric cardiac surgery. J Am Soc Nephrol 22:1737–1747CrossRefPubMedPubMedCentral Parikh CR, Devarajan P, Zappitelli M, Sint K, Thiessen-Philbrook H, Li S, Kim RW, Koyner JL, Coca SG, Edelstein CL, Shlipak MG, Garg AX, Krawczeski CD (2011) Postoperative biomarkers predict acute kidney injury and poor outcomes after pediatric cardiac surgery. J Am Soc Nephrol 22:1737–1747CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Garimella PS, Jaber BL, Tighiouart H, Liangos O, Bennett MR, Devarajan P, El-Achkar TM, Sarnak MJ (2017) Association of Preoperative Urinary Uromodulin with AKI after Cardiac Surgery. Clin J am Soc Nephrol 12:10–18CrossRefPubMed Garimella PS, Jaber BL, Tighiouart H, Liangos O, Bennett MR, Devarajan P, El-Achkar TM, Sarnak MJ (2017) Association of Preoperative Urinary Uromodulin with AKI after Cardiac Surgery. Clin J am Soc Nephrol 12:10–18CrossRefPubMed
13.
Zurück zum Zitat Tamm I, Horsfall FL Jr (1952) A mucoprotein derived from human urine which reacts with influenza, mumps, and Newcastle disease viruses. J Exp Med 95:71–97CrossRefPubMedPubMedCentral Tamm I, Horsfall FL Jr (1952) A mucoprotein derived from human urine which reacts with influenza, mumps, and Newcastle disease viruses. J Exp Med 95:71–97CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Pruijm M, Ponte B, Ackermann D, Paccaud F, Guessous I, Ehret G, Pechère-Bertschi A, Vogt B, Mohaupt MG, Martin P-Y, Youhanna SC, Nägele N, Vollenweider P, Waeber G, Burnier M, Devuyst O, Bochud M (2016) Associations of Urinary Uromodulin with Clinical Characteristics and Markers of Tubular Function in the General Population. Clin J Am Soc Nephrol 11:70–80CrossRefPubMed Pruijm M, Ponte B, Ackermann D, Paccaud F, Guessous I, Ehret G, Pechère-Bertschi A, Vogt B, Mohaupt MG, Martin P-Y, Youhanna SC, Nägele N, Vollenweider P, Waeber G, Burnier M, Devuyst O, Bochud M (2016) Associations of Urinary Uromodulin with Clinical Characteristics and Markers of Tubular Function in the General Population. Clin J Am Soc Nephrol 11:70–80CrossRefPubMed
15.
Zurück zum Zitat El-Achkar TM, Wu XR, Rauchman M, McCracken R, Kiefer S, Dagher PC (2008) Tamm-Horsfall protein protects the kidney from ischemic injury by decreasing inflammation and altering TLR4 expression. Am J Physiol Renal Physiol 295:F534–F544CrossRefPubMedPubMedCentral El-Achkar TM, Wu XR, Rauchman M, McCracken R, Kiefer S, Dagher PC (2008) Tamm-Horsfall protein protects the kidney from ischemic injury by decreasing inflammation and altering TLR4 expression. Am J Physiol Renal Physiol 295:F534–F544CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Hart TC, Gorry MC, Hart PS, Woodard AS, Shihabi Z, Sandhu J, Shirts B, Xu L, Zhu H, Barmada MM, Bleyer AJ (2002) Mutations of the UMOD gene are responsible for medullary cystic kidney disease 2 and familial juvenile hyperuricaemic nephropathy. J Med Genet 39:882–892CrossRefPubMedPubMedCentral Hart TC, Gorry MC, Hart PS, Woodard AS, Shihabi Z, Sandhu J, Shirts B, Xu L, Zhu H, Barmada MM, Bleyer AJ (2002) Mutations of the UMOD gene are responsible for medullary cystic kidney disease 2 and familial juvenile hyperuricaemic nephropathy. J Med Genet 39:882–892CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Edwards N, Olinger E, Adam J, Kelly M, Schiano G, Ramsbottom SA, Sandford R, Devuyst O, Sayer JA (2017) A novel homozygous UMOD mutation reveals gene dosage effects on uromodulin processing and urinary excretion. Nephrol Dial Transplant. https://doi.org/10.1093/ndt/gfx066 Edwards N, Olinger E, Adam J, Kelly M, Schiano G, Ramsbottom SA, Sandford R, Devuyst O, Sayer JA (2017) A novel homozygous UMOD mutation reveals gene dosage effects on uromodulin processing and urinary excretion. Nephrol Dial Transplant. https://​doi.​org/​10.​1093/​ndt/​gfx066
18.
Zurück zum Zitat Rampoldi L, Scolari F, Amoroso A, Ghiggeri G, Devuyst O (2011) The rediscovery of uromodulin (Tamm-Horsfall protein): from tubulointerstitial nephropathy to chronic kidney disease. Kidney Int 80:338–347CrossRefPubMed Rampoldi L, Scolari F, Amoroso A, Ghiggeri G, Devuyst O (2011) The rediscovery of uromodulin (Tamm-Horsfall protein): from tubulointerstitial nephropathy to chronic kidney disease. Kidney Int 80:338–347CrossRefPubMed
19.
Zurück zum Zitat Jenkins KJ (2004) Risk adjustment for congenital heart surgery: the RACHS-1 method. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 7:180–184CrossRefPubMed Jenkins KJ (2004) Risk adjustment for congenital heart surgery: the RACHS-1 method. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 7:180–184CrossRefPubMed
20.
Zurück zum Zitat Devarajan P (2013) Pediatric Acute kidney injury: Different From Acute Renal Failure But How And Why. Curr Pediatr Rep 1:34–40CrossRefPubMed Devarajan P (2013) Pediatric Acute kidney injury: Different From Acute Renal Failure But How And Why. Curr Pediatr Rep 1:34–40CrossRefPubMed
21.
Zurück zum Zitat Greenberg JH, Zappitelli M, Devarajan P, Thiessen-Philbrook HR, Krawczeski C, Li S, Garg AX, Coca S, Parikh CR (2016) Kidney Outcomes 5 Years After Pediatric Cardiac Surgery: The TRIBE-AKI Study. JAMA Pediatr 170:1071–1078CrossRefPubMedPubMedCentral Greenberg JH, Zappitelli M, Devarajan P, Thiessen-Philbrook HR, Krawczeski C, Li S, Garg AX, Coca S, Parikh CR (2016) Kidney Outcomes 5 Years After Pediatric Cardiac Surgery: The TRIBE-AKI Study. JAMA Pediatr 170:1071–1078CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Lim CC, Tan CS, Chia CM, Tan AK, Choo JC, Kaushik M, Tan HK (2015) Long-Term Risk of Progressive Chronic Kidney Disease in Patients with Severe Acute kidney injury Requiring Dialysis after Coronary Artery Bypass Surgery. Cardiorenal Med 5:157–163CrossRefPubMedPubMedCentral Lim CC, Tan CS, Chia CM, Tan AK, Choo JC, Kaushik M, Tan HK (2015) Long-Term Risk of Progressive Chronic Kidney Disease in Patients with Severe Acute kidney injury Requiring Dialysis after Coronary Artery Bypass Surgery. Cardiorenal Med 5:157–163CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat Hsu CY, Hsu RK, Yang J, Ordonez JD, Zheng S, Go AS (2016) Elevated BP after AKI. J Am Soc Nephrol 27:914–923CrossRefPubMed Hsu CY, Hsu RK, Yang J, Ordonez JD, Zheng S, Go AS (2016) Elevated BP after AKI. J Am Soc Nephrol 27:914–923CrossRefPubMed
25.
Zurück zum Zitat Serafini-Cessi F, Malagolini N, Cavallone D (2003) Tamm-Horsfall glycoprotein: biology and clinical relevance. Am J Kidney Dis 42:658–676CrossRefPubMed Serafini-Cessi F, Malagolini N, Cavallone D (2003) Tamm-Horsfall glycoprotein: biology and clinical relevance. Am J Kidney Dis 42:658–676CrossRefPubMed
26.
Zurück zum Zitat Hard K, Van Zadelhoff G, Moonen P, Kamerling JP, Vliegenthart FG (1992) The Asn-linked carbohydrate chains of human Tamm-Horsfall glycoprotein of one male. Novel sulfated and novel N-acetylgalactosamine-containing N-linked carbohydrate chains. Eur J Biochem 209:895–915CrossRefPubMed Hard K, Van Zadelhoff G, Moonen P, Kamerling JP, Vliegenthart FG (1992) The Asn-linked carbohydrate chains of human Tamm-Horsfall glycoprotein of one male. Novel sulfated and novel N-acetylgalactosamine-containing N-linked carbohydrate chains. Eur J Biochem 209:895–915CrossRefPubMed
27.
Zurück zum Zitat Kumar S (2007) Mechanism of injury in uromodulin-associated kidney disease. J Am Soc Nephrol 18:10–12CrossRefPubMed Kumar S (2007) Mechanism of injury in uromodulin-associated kidney disease. J Am Soc Nephrol 18:10–12CrossRefPubMed
28.
Zurück zum Zitat El-Achkar TM, McCracken R, Liu Y, Heitmeier MR, Bourgeois S, Ryerse J, Wu XR (2013) Tamm-Horsfall protein translocates to the basolateral domain of thick ascending limbs, interstitium, and circulation during recovery from acute kidney injury. Am J Physiol Renal Physiol 304:F1066–F1075CrossRefPubMedPubMedCentral El-Achkar TM, McCracken R, Liu Y, Heitmeier MR, Bourgeois S, Ryerse J, Wu XR (2013) Tamm-Horsfall protein translocates to the basolateral domain of thick ascending limbs, interstitium, and circulation during recovery from acute kidney injury. Am J Physiol Renal Physiol 304:F1066–F1075CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat El-Achkar TM, McCracken R, Rauchman M, Heitmeier MR, Al-Aly Z, Dagher PC, Wu XR (2011) Tamm-Horsfall protein-deficient thick ascending limbs promote injury to neighboring S3 segments in an MIP-2-dependent mechanism. Am J Physiol Renal Physiol 300:F999–1007CrossRefPubMedPubMedCentral El-Achkar TM, McCracken R, Rauchman M, Heitmeier MR, Al-Aly Z, Dagher PC, Wu XR (2011) Tamm-Horsfall protein-deficient thick ascending limbs promote injury to neighboring S3 segments in an MIP-2-dependent mechanism. Am J Physiol Renal Physiol 300:F999–1007CrossRefPubMedPubMedCentral
30.
Zurück zum Zitat Askenazi DJ, Koralkar R, Hundley HE, Montesanti A, Parwar P, Sonjara S, Ambalavanan N (2012) Urine biomarkers predict acute kidney injury in newborns. J Pediatr 161:270–275 e271CrossRefPubMedPubMedCentral Askenazi DJ, Koralkar R, Hundley HE, Montesanti A, Parwar P, Sonjara S, Ambalavanan N (2012) Urine biomarkers predict acute kidney injury in newborns. J Pediatr 161:270–275 e271CrossRefPubMedPubMedCentral
31.
Zurück zum Zitat Schlatzer D, Maahs DM, Chance MR, Dazard JE, Li X, Hazlett F, Rewers M, Snell-Bergeon JK (2012) Novel urinary protein biomarkers predicting the development of microalbuminuria and renal function decline in type 1 diabetes. Diabetes care 35:549–555CrossRefPubMedPubMedCentral Schlatzer D, Maahs DM, Chance MR, Dazard JE, Li X, Hazlett F, Rewers M, Snell-Bergeon JK (2012) Novel urinary protein biomarkers predicting the development of microalbuminuria and renal function decline in type 1 diabetes. Diabetes care 35:549–555CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat Youhanna S, Weber J, Beaujean V, Glaudemans B, Sobek J, Devuyst O (2014) Determination of uromodulin in human urine: influence of storage and processing. Nephrol Dial Transplant 29:136–145CrossRefPubMed Youhanna S, Weber J, Beaujean V, Glaudemans B, Sobek J, Devuyst O (2014) Determination of uromodulin in human urine: influence of storage and processing. Nephrol Dial Transplant 29:136–145CrossRefPubMed
Metadaten
Titel
Preoperative levels of urinary uromodulin predict acute kidney injury after pediatric cardiopulmonary bypass surgery
verfasst von
Michael R. Bennett
Olivia Pyles
Qing Ma
Prasad Devarajan
Publikationsdatum
23.10.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
Pediatric Nephrology / Ausgabe 3/2018
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-017-3823-0

Weitere Artikel der Ausgabe 3/2018

Pediatric Nephrology 3/2018 Zur Ausgabe

Update Pädiatrie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.